Serotonin neural circuits for reward, punishment, and mood

Principal investigator: Dr Jeremiah Cohen

Institution: Johns Hopkins University School of Medicine

Location: USA

Funding Period: 2015-2017

Serotonin is widely associated with changes in mood and many antidepressants work by increasing the amount of serotonin in the brain.

But our understanding of how the chemical is involved in conditions like depression and anxiety at a cellular level remains limited.

MQ Fellow Dr Jeremiah Cohen used innovative techniques to explore the role that brain chemical serotonin plays in affecting mood.

The project

Jeremiah focused on understanding serotonin neural circuits involved in reward, punishment, and mood. The aim was to uncover how serotonergic neurons signal and how their activity influences decision-making and mood regulation, with the broader goal of informing future treatments for mental health disorders.

The process

The team used techniques from genetics and physiology to study serotonin neurons in mice. Their aim is to create a map of serotonin activity in the brain, which can then be related back to humans.

In particular researchers are looking at:

How serotonin is released during specific tasks
How serotonin acts in different parts of the brain
How serotonin affects emotional behaviour

The outcome

Jeremiah’s work shows for the first time that it is possible to track the behaviour of serotonin neurons in the brain, furthering our understanding of this complex system and paving the way for better treatments. Jeremish and his team found that neurons in the prefrontal cortex are reward history is tracked during dynamic decision-making. This signal could provide serotonin-releasing neurons with precisely the information they need to calculate recent reward rates, which may give us the ability in the future to target these neurons specifically and be able to regulate appropriate behaviour and mood.

Key Findings:

- Serotonergic neurons track reward rates and influence decision-making flexibility;
- Prefrontal cortex inputs are crucial for providing reward history information to serotonergic neurons;
- Developed new behavioural paradigms to study cognitive bias and punishment signalling;
- The research represents the first observations of identified serotonergic neurons during complex behaviours, laying the groundwork for future drug development targeting specific subsystems.

This project resulted in two additional funding grants to further Jeramiah’s research.

Papers published

Tian J, Huang R, Cohen JY, Osakada F, Kobak D, Machens CK, Callaway EM, Uchida N, Watabe-Uchida M. Distributed and Mixed Information in Monosynaptic Inputs to Dopamine Neurons. Neuron. 2016

The impact

The basis information that Jeremiah has uncovered will be fundamental in understanding the “nuts and bolts” of this important system.

As Jeremiah says: “I envision future drug development and other therapies based on theories of how the brain produces behaviour will rest heavily on these results.”

Scientific Impact:

- The findings form the basis for ongoing and future research in the lab;
- Techniques developed are being adopted by other labs, facilitating cross-species comparisons of serotonin neuron activity.

Societal Impact:

- - Over the long term, the research may lead to better drugs for mood disorders by targeting specific serotonin subsystems, potentially reducing side effects of current treatments;
  - No direct patient or public involvement in the research process, and no immediate societal impacts reported yet.

Career and Capacity Building:

MQ funding was critical in launching the lab’s research programme and led to the first publications from the lab;

Dr Jeremiah Cohen

Dr Jeremiah Cohen works at the Brain Science Institute and the Solomon H Snyder Department of Neuroscience at The John Hopkins School of Medicine. He focuses on the impact of neural circuits in the brain.